title: The role of arterial smooth muscle in vasorelaxation.
abstract: The concept of endothelium-derived relaxing factor (EDRF) implies that nitric oxide (NO) produced by NO synthase (NOS) in the endothelium in response to vasorelaxants such as acetylcholine (ACh) acts on the underlying vascular smooth muscle cells (VSMC) inducing vascular relaxation. The EDRF concept was derived from experiments on denuded blood vessel strips and, in frames of this concept, VSMC were regarded as passive recipients of NO from endothelial cells. However, it was later found that VSMC express NOS by themselves, but the principal question remained unanswered, is the NO generation by VSMC physiologically relevant? We hypothesized that the destruction of the vascular wall anatomical integrity by rubbing off the endothelial layer might increase vascular superoxides that, in turn, reduced the NO bioactivity as a relaxing factor. To test our hypothesis, we examined ACh-induced vasorelaxation under protection against oxidative stress and found that superoxide scavengers restored vasodilatory responses to ACh in endothelium-deprived blood vessels. These findings imply that VSMC can release NO in amounts sufficient to account for the vasorelaxatory response and challenge the concept of the obligatory role of endothelial cells in the relaxation of arterial smooth muscle.
authors.affiliation: Gerhard Domagk Institute of Pathology, University of Muenster, 48149 Muenster, Germany. Electronic address: buchwalo@uni-muenster.de.
authors.forename: Igor B
authors.initials: IB
authors.lastname: Buchwalow
authors.affiliation: Institute of Normal and Pathological Physiology, Slovak Academy of Sciences, Bratislava, Slovak Republic.
authors.forename: Sona
authors.initials: S
authors.lastname: Cacanyiova
authors.affiliation: Institute for Pharmacology und Toxicology, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Neumann
authors.affiliation: Gerhard Domagk Institute of Pathology, University of Muenster, 48149 Muenster, Germany.
authors.forename: Vera E
authors.initials: VE
authors.lastname: Samoilova
authors.affiliation: Gerhard Domagk Institute of Pathology, University of Muenster, 48149 Muenster, Germany.
authors.forename: Werner
authors.initials: W
authors.lastname: Boecker
authors.affiliation: Institute of Normal and Pathological Physiology, Slovak Academy of Sciences, Bratislava, Slovak Republic.
authors.forename: Frantisek
authors.initials: F
authors.lastname: Kristek
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D016166:Free Radical Scavengers / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D018384:Oxidative Stress; D013481:Superoxides / Q000378:metabolism; D014664:Vasodilation
chemical_list: D016166:Free Radical Scavengers; D013481:Superoxides; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D000109:Acetylcholine